Method for selecting compounds for treating ischemia-related cellular damage

Abstract

A method of screening for and treating subjects with a therapeutically effective amount of a compound that is effective in reducing cellular damage related to an ischemic condition, such as stroke or glaucoma. Test compounds are selected and therapeutically effective amount determined based on the relative efficacy of test compounds in preventing cell death in primary cultures of excitable cells, such as retinal ganglion cells, in vitro.

What is claimed is:  
     
       1. A method of screening test compounds as candidates for treating or preventing ischemia-related cellular damage, comprising 
       subjecting a purified primary culture of at least 75% retinal ganglion cells to an oxygen/glucose deprivation challenge sufficient to produce cell death in at least 25% of the retinal ganglion cells when examined at a selected time after the challenge,  
       exposing said cells to one or more test compounds to be screened,  
       examining the cells at such selected time after challenge for the presence of cell death, and  
       selecting the test compound as a candidate for treating ischemia-related cellular damage if the percentage of dead cells in the test culture is substantially less than that of a control culture.  
     
     
       2. The method of  claim 1 , wherein said retinal ganglion cells are at least 80% of said purified primary culture. 
     
     
       3. The method of  claim 1 , wherein said retinal ganglion cells are at least 90% of said purified primary culture. 
     
     
       4. The method of  claim 1 , wherein said retinal ganglion cells are at least 99% of said purified primary culture. 
     
     
       5. The method of  claim 1 , wherein said examining is for the presence of apoptotic cell death. 
     
     
       6. The method of  claim 1 , wherein said examining is for the presence of necrotic cell death. 
     
     
       7. The method of  claim 1 , wherein said examining is for the presence of non-apoptotic, non-necrotic cell death. 
     
     
       8. The method of  claim 1 , wherein the test compound is calcium channel blocker. 
     
     
       9. The method of  claim 1 , wherein the test compound is an N-methyl-D-aspartate (NMDA receptor antagonist. 
     
     
       10. The method of  claim 1 , wherein the test compound is a bis-benzimidazole. 
     
     
       11. The method of  claim 1 , wherein said ischemia-related cellular damage is neuronal ischemia. 
     
     
       12. The method of  claim 11 , wherein said ischemia-related cellular damage is neuronal cell damage in the central nervous system associated with cerebral ischemia. 
     
     
       13. The method of  claim 1 , wherein the primary culture cells are purified by immunopanning.